- |||||||||| bictegravir (GS-9883) / Gilead, Tivicay (dolutegravir) / ViiV Healthcare
Review, Journal: Non-Nucleoside Reverse Transcriptase Inhibitors Join Forces with Integrase Inhibitors to Combat HIV. (Pubmed Central) - Jun 19, 2020
In the treatment of acquired immune deficiency syndrome (AIDS), the diarylpyrimidine (DAPY) analogs etravirine (ETR) and rilpivirine (RPV) have been widely effective against human immunodeficiency virus (HIV) variants that are resistant to other non-nucleoside reverse transcriptase inhibitors (NNRTIs)...In a separate development, HIV integrase strand transfer inhibitors (INSTIs) have shown efficacy in treating AIDS, including raltegravir (RAL), elvitegravir (EVG), cabotegravir (CAB), bictegravir (BIC), and dolutegravir (DTG)...Here, highly resistant emergent mutations and efficacy data on these novel treatments are reviewed. Overall, ETR or RPV, in combination with INSTIs, may be treatments of choice as long-term maintenance therapies that optimize efficacy, adherence, and safety.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
Journal: Antiretroviral-Mediated Microglial Activation Involves Dysregulated Autophagy and Lysosomal Dysfunction. (Pubmed Central) - Jun 18, 2020
Taken together, our findings suggest a novel mechanism by which cART impairs lysosomal functioning, resulting in dysregulated autophagy and increased neuroinflammation. Interventions aimed at lysosome protection could likely be envisioned as promising therapeutic targets for abrogating cART-mediated microglia activation, which in turn, could thus be considered as adjunctive therapeutics for the treatment of HAND pathogenesis.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
Review, Journal: Curbing the rise of HIV drug resistance in low-income and middle-income countries: the role of dolutegravir-containing regimens. (Pubmed Central) - Jun 12, 2020
Finally, clinical management of patients with confirmed virological failure on a dolutegravir-based regimen can pose challenges because of uncertainty around whether dolutegravir resistance has actually developed and switching is needed, or whether only interventions to improve adherence without switching are sufficient. These considerations should be addressed to consolidate expected gains from widespread introduction of dolutegravir in low-income and middle-income countries.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
Journal: A lesson to learn from dolutegravir roll-out. (Pubmed Central) - Jun 12, 2020
These considerations should be addressed to consolidate expected gains from widespread introduction of dolutegravir in low-income and middle-income countries. No abstract available
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare, abacavir / Generic mfg.
Clinical, Journal, Adverse events: Integrase strand transfer inhibitors and neuropsychiatric adverse events in a large prospective cohort. (Pubmed Central) - Jun 8, 2020
Although discontinuation for side effects was less frequent with dolutegravir than with boosted elvitegravir, discontinuation for NPAEs, although rare (2.7%), was more frequent with dolutegravir. No patient characteristic was found to be associated with these side effects in this very large population.
- |||||||||| lamivudine / Generic mfg., Tivicay (dolutegravir) / ViiV Healthcare
Clinical, P3 data, Journal, Head-to-Head: Bictegravir combined with emtricitabine and tenofovir alafenamide versus dolutegravir, abacavir, and lamivudine for initial treatment of HIV-1 infection: week 96 results from a randomised, double-blind, multicentre, phase 3, non-inferiority trial. (Pubmed Central) - Jun 5, 2020
P3
National Institutes of Health, Gilead Sciences. These week 96 data support bictegravir, emtricitabine, and tenofovir alafenamide as a safe, well tolerated, and durable treatment for people living with HIV-1 with no emergent resistance.
- |||||||||| Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide) / Gilead, Tivicay (dolutegravir) / ViiV Healthcare
Clinical, P3 data, Journal, Head-to-Head: Co-formulated bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir with emtricitabine and tenofovir alafenamide for initial treatment of HIV-1 infection: week 96 results from a randomised, double-blind, multicentre, phase 3, non-inferiority trial. (Pubmed Central) - Jun 5, 2020
P3
These week 96 data support bictegravir, emtricitabine, and tenofovir alafenamide as a safe, well tolerated, and durable treatment for people living with HIV-1 with no emergent resistance. These week 96 data support bictegravir, emtricitabine, and tenofovir alafenamide as a safe, well tolerated, and durable treatment for people living with chronic HIV.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
Clinical, Journal: Lung Transplant in HIV-Infected Patients. Single Centre Experience. (Pubmed Central) - May 30, 2020
No abstract available The experience of the first five VIH LT patients in Spain shows that LT is feasible without increasing the risk of infectious or immunological complications.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
Trial completion date, Trial suspension, Trial primary completion date: Dolutegravir in Reservoirs (clinicaltrials.gov) - May 29, 2020
P=N/A, N=40, Suspended,
The lack of additional changes when the drugs were used in combination, and the lower impact in cases of previous chronic kidney disease, suggest that there are compensatory mechanisms for creatinine secretion. Trial completion date: Jun 2020 --> Oct 2020 | Recruiting --> Suspended | Trial primary completion date: Jun 2020 --> Oct 2020
- |||||||||| Prezcobix (darunavir/cobicistat) / Gilead, J&J, Tivicay (dolutegravir) / ViiV Healthcare
Clinical, Journal: Multidrug-resistant HIV viral rebound during early syphilis: a case report. (Pubmed Central) - May 28, 2020
Trial completion date: Jun 2020 --> Oct 2020 | Recruiting --> Suspended | Trial primary completion date: Jun 2020 --> Oct 2020 This case shows that early syphilis may cause an HIV RNA rebound in patients under stable virological control with the potential of transmitting an extensively drug-resistant virus.
- |||||||||| bictegravir (GS-9883) / Gilead, Tivicay (dolutegravir) / ViiV Healthcare
Clinical, PK/PD data, Review, Journal: Pharmacokinetics of HIV-Integrase Inhibitors During Pregnancy: Mechanisms, Clinical Implications and Knowledge Gaps. (Pubmed Central) - May 25, 2020
Despite increased clearance, for raltegravir 400 mg twice daily and dolutegravir 50 mg once daily, exposure during pregnancy seems adequate; however, for elvitegravir, the proposed minimal effective concentration is not reached during pregnancy...The pharmacokinetics of bictegravir and cabotegravir, which are under development, have not yet been evaluated in pregnant women...To further optimize antiretroviral treatment in pregnant women, studies need to unravel the underlying mechanisms behind the changes in the pharmacokinetics of HIV-integrase inhibitors during pregnancy. More knowledge on altered pharmacokinetics during pregnancy and the underlying mechanisms contribute to the development of effective and safe antiretroviral therapy for HIV-infected pregnant women.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
Clinical, Journal: Inclusion of pregnant women in antiretroviral drug research: what is needed to move forwards? (Pubmed Central) - May 21, 2020
Through more vigorous action, regulatory bodies could responsibly overcome reluctance to include pregnant women in drug trials. Funders, researchers and programme implementers need to be galvanized to progressively include pregnant women in research - the use of newer, more effective drugs in women is at stake (349).
- |||||||||| lamivudine / Generic mfg., Tivicay (dolutegravir) / ViiV Healthcare
Clinical, Journal, Monotherapy: Predictors of virological failure in HIV-1-infected patients switching to dolutegravir maintenance monotherapy. (Pubmed Central) - May 20, 2020
P4
A lower CD4 nadir, a longer time between HIV diagnosis and cART initiation, and a higher HIV DNA copy number at the time of DTG monotherapy initiation were associated with VF. While there clearly is no future role for DTG monotherapy, ongoing and future studies on the efficacy of maintenance dual therapy (e.g. DTG lamivudine) may have to take these variables into account in their study design and analysis.
- |||||||||| Journal: Influence of hair treatments on detection of antiretrovirals by mass spectrometry imaging. (Pubmed Central) - May 19, 2020
While FTC was undetectable in the treated portion of these hair strands, ARVs coadministered with FTC remained detectable in hair strands after treatment. We conclude that IR-MALDESI MSI can be used when measuring adherence to ARV therapy, provided that ARVs other than FTC are targeted in people using hair treatments.
- |||||||||| bictegravir (GS-9883) / Gilead, Pifeltro (doravirine) / Merck (MSD), Tivicay (dolutegravir) / ViiV Healthcare
Clinical, P3 data, Journal: Phase 3 trials of new antiretrovirals are not representative of the global HIV epidemic. (Pubmed Central) - May 16, 2020
The present study compared race and sex demographics of phase 3 RCTs of dolutegravir (DTG), bictegravir (BIC) and tenofovir alafenamide (TAF) with global HIV epidemic demography...Summary race and sex demographic data for 10 phase 3 trials of DTG (n = 7714), four of BIC (n = 2307), eight of TAF (n = 7573) and two of doravirine (DOR) (n = 1407) were extracted from ClinicalTrials.gov...HIV trials should be located in regions representing the global epidemic with no sex-based selection. Trials should aim for at least 50% female and 50% non-white recruitment to properly provide safety information.
- |||||||||| Descovy (emtricitabine/tenofovir alafenamide) / Gilead, Tivicay (dolutegravir) / ViiV Healthcare
Trial completion date, Trial primary completion date: Rapid HIV Treatment Initiation, Access and Engagement in Care (clinicaltrials.gov) - May 11, 2020
P2, N=20, Recruiting,
Our results indicate that while INSTIs do exhibit the capacity to antagonize MC4R, this occurs at concentrations well above predicted clinical exposure and is thus an implausible explanation for INSTI-associated weight gain. Trial completion date: May 2020 --> Sep 2020 | Trial primary completion date: May 2020 --> Sep 2020
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
Journal: Treatment of Central Nervous System Manifestations of HIV in the Current Era. (Pubmed Central) - Apr 30, 2020
Efavirenz has been well-recognized for its neuropsychiatric adverse effects and potential for causing sleep disturbances. Similar concerns have recently been raised with integrase inhibitors, especially dolutegravir and raltegravir, although further studies are needed to determine the risks for clinically relevant neuropsychiatric side effects from these medications, given their overall high potency and proven success in treating systemic HIV.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare, abacavir/lamivudine / Generic mfg.
Journal, HEOR: De-simplifying single-tablet antiretroviral treatments: uptake, risks and cost savings. (Pubmed Central) - Apr 29, 2020
Similar concerns have recently been raised with integrase inhibitors, especially dolutegravir and raltegravir, although further studies are needed to determine the risks for clinically relevant neuropsychiatric side effects from these medications, given their overall high potency and proven success in treating systemic HIV. Reliance on altruism, while respecting patient autonomy, achieved de-simplification in > 50% of patients approached, and generated immediate cost savings with no increased risk of adverse events, viral breakthrough or resistance.
- |||||||||| Prezista (darunavir) / J&J, Tivicay (dolutegravir) / ViiV Healthcare
Clinical, Journal: Effectiveness of Once-Daily Dolutegravir plus Boosted Darunavir as a Switch Strategy in Human Immunodeficiency Virus-Infected, Heavily Treated Patients. (Pubmed Central) - Apr 29, 2020
Reliance on altruism, while respecting patient autonomy, achieved de-simplification in > 50% of patients approached, and generated immediate cost savings with no increased risk of adverse events, viral breakthrough or resistance. In this cohort of heavily treated, HIV-infected patients with virologic suppression, switching to the combination of DTG+DRV/b was a convenient regimen that was highly effective and had good tolerability.
- |||||||||| bictegravir (GS-9883) / Gilead, Tivicay (dolutegravir) / ViiV Healthcare
Journal: Integrase Inhibitors: After 10 Years of Experience, Is the Best Yet to Come? (Pubmed Central) - Apr 29, 2020
Since that time, several other INSTIs have been introduced including elvitegravir, dolutegravir, and, most recently, bictegravir, that have shown great utility as part of antiretroviral regimens in both treatment-naive and treatment-experienced patients...After 10 years of experience with INSTIs, newer agents are on the horizon such as cabotegravir and MK-2048 for potential use as either HIV pre-exposure prophylaxis or maintenance therapy. This review provides a brief overview of the INSTI class, including agents currently available and those still in development, reviews available data from both completed and ongoing clinical trials, and outlines simplification strategies using INSTIs.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare, abacavir / Generic mfg.
Journal: Switch to dolutegravir is well tolerated in Thais with HIV infection. (Pubmed Central) - Apr 29, 2020
Incident hepatitis C virus infection was a driver of liver-related AEs leading to discontinuations. In populations at risk, regular testing for hepatitis C virus during ART is recommended to anticipate possible AEs, guide management and improve safety.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
Clinical, Journal: Optimizing responses to drug safety signals in pregnancy: the example of dolutegravir and neural tube defects. (Pubmed Central) - Apr 29, 2020
It requires the existence of appropriately designed surveillance systems with broad population coverage; data analyses that examine risk-benefit trade-offs in a variety of contexts; guidance to transform this risk-benefit balance into effective and agreed-upon policy; involvement of the affected community and other key stakeholders; and a communication plan for all levels of knowledge and complexity. Implementation of this proposed framework for responding to safety signals is needed to ensure that any drug used in pregnancy can be rapidly and appropriately evaluated should a serious safety alert arise.
- |||||||||| Mycobutin (rifabutin) / Pfizer, Lupin, rifampicin / Generic mfg., Tivicay (dolutegravir) / ViiV Healthcare
Clinical, Journal: Global access of rifabutin for the treatment of tuberculosis - why should we prioritize this? (Pubmed Central) - Apr 29, 2020
Rifabutin should be available globally as a first-line rifamycin in HIV co-infected individuals and as a switch option in cases of rifampicin associated ADRs. Further studies are needed to ascertain the utility of rifabutin in rifampicin-resistant rifabutin-susceptible TB.
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